Without limiting the scope of the invention, its background is described in connection with single molecule imaging.
Currently it is difficult and time consuming to measure the activity of single molecules at specific points in a biochemical pathway within a living cell. Such experiments are extremely important to both drug discovery and basic biological research. There is a large movement in the drug discovery field toward the area of high content cellular screening, which has become a valuable tool for understanding where in a cell a specific drug exerts its effects.
U.S. Pat. No. 7,318,907, issued to Stark, et al., teaches a surface plasmon enhanced illumination system, teaches methods and apparatus for producing small, bright nanometric light sources from apertures that are smaller than the wavelength of the emitted light. Light is directed at a surface layer of metal onto a light barrier structure that includes one or more apertures each of which directs a small spot of light onto a target. The incident light excites surface plasmons (electron density fluctuations) in the top metal surface layer and this energy couples through the apertures to the opposing surface where it is emitted as light from the apertures or from the rims of the apertures. Means are employed to prevent or severely limit the extent to which surface plasmons are induced on the surface at the aperture exit, thereby constraining the resulting emissions to small target areas. The resulting small spot illumination may be used to increase the resolution of microscopes and photolithographic processes, increase the storage capacity and performance of optical data storage systems, and analyze the properties of small objects such as protein and nucleic acid molecules and single cells.
U.S. Pat. No. 7,118,907, issued to Williams, teaches a single molecule detection systems and methods. Briefly, a microfluidic system is provided that includes a substrate, a first microchannel disposed in the substrate for providing a reactant to a reaction zone, a second microchannel disposed in the substrate, and a third microchannel disposed in the substrate, the third microchannel providing fluid communication between the first and second microchannels. The system also typically includes first and second electrodes, positioned at opposite ends of the second microchannel, for providing an electric field within the second microchannel. In operation, when the reactant is in the reaction zone, a reaction product is produced having a net electric charge different from the electric charge of the reactant.
Finally, U.S. Pat. No. 7,298,549, issued to Muller teaches a confocal microscope has a specimen holding device for holding a specimen. The specimen is illuminated by an illuminating unit. An optics unit serves to direct radiation produced by the illuminating unit toward the specimen and to direct the radiation emitted by the specimen toward a detector unit. The confocal microscope also comprises an aperture diaphragm that is placed in the beam path in front of the detector unit. In addition, a focusing lens is provided in the beam path in front of the aperture diaphragm. The focusing lens can be moved in order to adjust the confocal microscope, for example, in order to compensate for thermal stresses.